Comparative efficacy of opioid and non-opioid analgesics in labor pain management: A network meta-analysis

Background Effective labor pain management is crucial for parturient well-being, as it can improve the delivery experience of pregnant women and reduce anxiety and tension. This systematic review and network meta-analysis compared the efficacy and safety of various analgesics, classified by drug category and individual treatment methods, for labor pain control. Methods A comprehensive literature search was conducted in Pubmed, EMBASE, Cochrane Library, and Web of Science databases. All searches commenced from the database’s inception to the date of the literature search (May 31, 2023). The Cochrane Risk of Bias 2 tool assessed study bias risk. Network meta-analyses using a random-effects model and odds ratios (ORs) with 95% confidence intervals (CIs) were performed. Results Fifteen randomized controlled trials evaluating analgesic interventions in ASA I or II parturients were included. Combination therapies (OR: 5.81; 95% CI, 3.76–7.84; probability: 60%) and non-opioid analgesics (OR: 5.61; 95% CI, 2.91–8.30; probability: 39.2%) were superior to placebo for labor pain relief. Specifically, dexmedetomidine/ropivacaine/sufentanil (OR: 7.32; 95% CI, 2.73–11.89; probability: 40.6%) and dexmedetomidine/ropivacaine (OR: 6.50; 95% CI, 2.51–10.33; probability: 11.9%) combinations, bupivacaine/fentanyl and ropivacaine/sufentanil combinations, and remifentanil monotherapy showed improved analgesic efficacy versus placebo. Dexmedetomidine/ropivacaine reduced parturient nausea and vomiting versus alternatives. Conclusion Non-opioids, opioids and combinations thereof effectively relieved labor pain. In addition, dexmedetomidine/ropivacaine combination demonstrated analgesic efficacy and lower nausea and vomiting incidence.


Rationale
Describe the rationale for the review in the context of what is already known, including mention of why a network metaanalysis has been conducted.

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Objectives Provide an explicit statement of questions being addressed, with reference to participants, interventions, comparisons, outcomes, and study design (PICOS).

Protocol and registration
Indicate whether a review protocol exists and if and where it can be accessed (e.g., Web address); and, if available, provide registration information, including registration number.

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Eligibility criteria Specify study characteristics (e.g., PICOS, length of follow-up) and report characteristics (e.g., years considered, language, publication status) used as criteria for eligibility, giving rationale.Clearly describe eligible treatments included in the treatment network, and note whether any have been clustered or merged into the same node (with justification). 6 Information sources Describe all information sources (e.g., databases with dates of coverage, contact with study authors to identify additional studies) in the search and date last searched.

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Search Present full electronic search strategy for at least one database, including any limits used, such that it could be repeated.

Appendix A
Study selection 9 State the process for selecting studies (i.e., screening, eligibility, included in systematic review, and, if applicable, included in the meta-analysis).

Data collection process 10
Describe method of data extraction from reports (e.g., piloted forms, independently, in duplicate) and any processes for obtaining and confirming data from investigators.

Data items 11
List and define all variables for which data were sought (e.g., PICOS, funding sources) and any assumptions and simplifications made.

S1
Describe methods used to explore the geometry of the treatment network under study and potential biases related to it.This should include how the evidence base has been graphically summarized for presentation, and what characteristics were compiled and used to describe the evidence base to readers.

Risk of bias within individual studies 12
Describe methods used for assessing risk of bias of individual studies (including specification of whether this was done at the study or outcome level), and how this information is to be used in any data synthesis.

Summary measures 13
State the principal summary measures (e.g., risk ratio, difference in means).Also describe the use of additional summary measures assessed, such as treatment rankings and surface under the cumulative ranking curve (SUCRA) values, as well as modified approaches used to present summary findings from meta-analyses.

Planned methods of analysis 14
Describe the methods of handling data and combining results of studies for each network meta-analysis.This should include, but not be limited to: • Handling of multi-arm trials; • Selection of variance structure; • Selection of prior distributions in Bayesian analyses; and • Assessment of model fit.

S2
Describe the statistical methods used to evaluate the agreement of direct and indirect evidence in the treatment network(s) studied.Describe efforts taken to address its presence when found.

Risk of bias across studies 15
Specify any assessment of risk of bias that may affect the cumulative evidence (e.g., publication bias, selective reporting within studies).

Additional analyses 16
Describe methods of additional analyses if done, indicating which were pre-specified.This may include, but not be limited to, the following: • Sensitivity or subgroup analyses; • Meta-regression analyses; • Alternative formulations of the treatment network; and • Use of alternative prior distributions for Bayesian analyses (if applicable).

Study selection 17
Give numbers of studies screened, assessed for eligibility, and included in the review, with reasons for exclusions at each stage, ideally with a flow diagram.

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Presentation of network structure

S3
Provide a network graph of the included studies to enable visualization of the geometry of the treatment network.† Authors may wish to plan for use of appendices to present all relevant information in full detail for items in this section.

Comparative Efficacy of Labor Analgesia: A Network Meta-Analysis
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Review question
What is the optimal pharmacological intervention for labor pain management?More specifically, (1) What are the most effective drugs for maternal analgesia.
(2) Is there a difference in efficacy between single drug therapy and combination therapy for maternal analgesia.
(3) Which drugs have minimal impact on labor and have fewer side effects for maternal analgesia.

Searches
The PubMed, EMBASE, Web of Science and the Cochrane Library databases will be searched using terms such as "Labor Pain"and "epidural analgesia".
Publication period is 1970 ~ 2022.A comparison of the efficacy of epidural, intrathecal, and intravenous analgesia in postpartum women, with the exclusion of drugs used for test dosing.

Comparator(s)/control
Where relevant, give details of the alternatives against which the main subject/topic of the review will be compared (e.g.another intervention or a non-exposed control group).The preferred format includes details of both inclusion and exclusion criteria.
We will include studies that have no treatment control group or condition, or that use a standard management.This may include self-control and crossover studies.

Revision note
The article has been completed but not published.
The record owner confirms that the information they have supplied for this submission is accurate and complete and they understand that deliberate provision of inaccurate information or omission of data may be construed as scientific misconduct.
The record owner confirms that they will update the status of the review when it is completed and will add publication details in due course.

Figure
Figure 2B, 3B, 4B, 5B Summary of network geometryS4Provide a brief overview of characteristics of the treatment network.This may include commentary on the abundance of trials and randomized patients for the different interventions and pairwise comparisons in the network, gaps of evidence in the treatment network, and potential biases reflected by the network structure.
that are full text and published in peer-reviewed journals Exclusions: -Non-experimental studies -Studies that are abstract or poster form only -Studies that did not obtain ethics approval or IRB -Case studies with less than 10 patients -Studies that did not have target extraction data in the text and attachments Page: 1 / 5 PROSPERO International prospective register of systematic reviews Condition or domain being studied Parturients who are classified as American Society of Anesthesiologists (ASA) Class I or II.The result can be expressed as Analgesic Efficacy.Participants/population Inclusion criteria: Parturients classified as American Society of Anesthesiologists (ASA) Grade I or II, In labor and With no known fetal abnormalities.Exclusion criteria: Known drug allergy, Obstetric complications, Preeclampsia, Contraindications to anesthesia, Abnormal liver or kidney function, Abnormal blood function, and Drug dependence Intervention(s), exposure(s) Comment on the validity of the assumptions, such as transitivity and consistency.Comment on any concerns regarding network geometry (e.g., avoidance of certain comparisons).Conclusions 26 Provide a general interpretation of the results in the context of other evidence, and implications for future research.
Appendix B Synthesis of results 21Present results of each meta-analysis done, including confidence/credible intervals.In larger networks, authors may focus on comparisons versus a particular comparator (e.g.placebo or standard care), with full findings presented in an appendix.League tables and forest plots may be considered to summarize pairwise comparisons.If additional summary measures were explored (such as treatment rankings), these should also be presented.22Limitations25 Discuss limitations at study and outcome level (e.g., risk of bias), and at review level (e.g., incomplete retrieval of identified research, reporting bias).* Text in italics indicateS wording specific to reporting of network meta-analyses that has been added to guidance from the PRISMA statement.